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- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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- Seifahrt, A., et al.
(författare)
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Observation and modelling of dusty, low gravity L, and M dwarfs
- 2009
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Ingår i: COOL STARS, STELLAR SYSTEMS AND THE SUN: Proceedings of the 15th Cambridge Workshop on Cool Stars, Stellar Systems and the Sun. - : AIP. - 9780735406278 ; , s. 283-290
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Konferensbidrag (refereegranskat)abstract
- Observational facilities allow now the detection of optical and IR spectra of young M- and L-dwarfs. This enables empirical comparisons with old M- and L- dwarfs, and detailed studies in comparison with synthetic spectra. While classical stellar atmosphere physics seems perfectly appropriate for old M-dwarfs, more physical and chemical processes, cloud formation in particular, needs to be modelled in the substellar regime to allow a detailed spectral interpretation. Not much is known so far about the details of the inset of cloud formation at the spectral transition region between M and L dwarfs. Furthermore there is observational evidence for diversity in the dust properties of objects having the same spectral type. Do we understand these differences? The question is also how young M- and L-dwarfs need to be classified, which stellar parameter do they have and whether degenerations in the stellar parameter space due to the changing atmosphere physics are present, like in the L-T transition region. The Splinter was driven by these questions which we will use to encourage interactions between observation and theory. Given the recent advances, both in observations and spectral modelling, an intensive discussion between observers and theoreticians will create new synergies in our field.
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- Yu, X., et al.
(författare)
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Association of UCP2 - 866 G/A polymorphism with chronic inflammatory diseases
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:6, s. 601-605
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Tidskriftsartikel (refereegranskat)abstract
- We reported earlier that two mitochondrial gene polymorphisms, UCP2 -866 G/A (rs659366) and mtDNA nt13708 G/A (rs28359178), are associated with multiple sclerosis (MS). Here we aim to investigate whether these functional polymorphisms contribute to other eight chronic inflammatory diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener' granulomatosis (WG), Churg-Strauss syndrome (CSS), Crohn's disease (CD), ulcerative colitis (UC), primary sclerosing cholangitis (PSC) and psoriasis. Compared with individual control panels, the UCP2 -866 G/A polymorphism was associated with RA and SLE, and the mtDNA nt13708 G/A polymorphism with RA. Compared with combined controls, the UCP2 -866 G/A polymorphism was associated with SLE, WG, CD and UC. When all eight disease panels and the original MS panel were combined in a meta-analysis, the UCP2 was associated with chronic inflammatory diseases in terms of either alleles (odds ratio (OR)=0.91, 95% confidence interval (95% CI): 0.86-0.96), P=0.0003) or genotypes (OR=0.88, (95% CI: 0.82-0.95), P=0.0008), with the -866A allele associated with a decreased risk to diseases. As the -866A allele increases gene expression, our findings suggest a protective role of the UCP2 protein in chronic inflammatory diseases.
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